rs838090

Variant names:

• chr2-119239583-T-C
• rs838090
• NM_182915.3:c.23-5906T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182915.3(STEAP3):​c.23-5906T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,150 control chromosomes in the GnomAD database, including 9,941 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9941 hom., cov: 33)
• Consequence: STEAP3 NM_182915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423
• Publications: 12 publications found

Genes affected

STEAP3 (HGNC:24592): (STEAP3 metalloreductase) This gene encodes a multipass membrane protein that functions as an iron transporter. The encoded protein can reduce both iron (Fe3+) and copper (Cu2+) cations. This protein may mediate downstream responses to p53, including promoting apoptosis. Deficiency in this gene can cause anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

STEAP3 Gene-Disease associations (from GenCC):

• severe congenital hypochromic anemia with ringed sideroblasts

  Inheritance: AD, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182915.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP3	NM_182915.3	MANE Select	c.23-5906T>C		intron	N/A	NP_878919.2	Q658P3-2
	STEAP3	NM_001008410.2		c.-8-5906T>C		intron	N/A	NP_001008410.1	Q658P3-1
	STEAP3	NM_018234.3		c.-9+153T>C		intron	N/A	NP_060704.2	Q658P3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STEAP3	ENST00000393110.7	TSL:1 MANE Select	c.23-5906T>C		intron	N/A	ENSP00000376822.2	Q658P3-2
	STEAP3	ENST00000393106.6	TSL:1	c.-9+153T>C		intron	N/A	ENSP00000376818.2	Q658P3-1
	STEAP3	ENST00000393107.2	TSL:1	c.-8-5906T>C		intron	N/A	ENSP00000376819.2	Q658P3-1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51683 AN: 152030 Hom.: 9932 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.340 AC: 51699 AN: 152150 Hom.: 9941 Cov.: 33 AF XY: 0.335 AC XY: 24904 AN XY: 74368

African (AFR) AF: 0.160 AC: 6658 AN: 41528

American (AMR) AF: 0.324 AC: 4952 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1366 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1706 AN: 5164

South Asian (SAS) AF: 0.319 AC: 1539 AN: 4824

European-Finnish (FIN) AF: 0.366 AC: 3871 AN: 10588

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30499 AN: 67964

Other (OTH) AF: 0.371 AC: 782 AN: 2110

Alfa AF: 0.415 Hom.: 58449

Bravo AF: 0.329

Asia WGS AF: 0.282 AC: 981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.54
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs838090;

hg19: chr2-119997159;

COSMIC: COSV61528320;

COSMIC: COSV61528320;